Comparative Effectiveness of Postdischarge Smoking Cessation Interventions for Hospital Patients

Key Points Question How can health systems most effectively provide smoking cessation treatment to patients after hospital discharge to promote long-term tobacco abstinence? Findings This randomized clinical trial of 1409 hospitalized smokers compared 2 models for delivering tobacco cessation treatment after discharge: health system–based care or referral to a community-based quitline. Health system–based care produced better treatment use and more tobacco abstinence throughout the 3 months of treatment but not 6 months after discharge. Meaning These findings suggest that continuing treatment beyond 3 months might have sustained end-of-treatment superiority of the health system–based model.

Other pilot work conducted by the research team.
Coordination of care by a tobacco coach increases use of proven quit aids. In a two-arm RCT of a proactive longitudinal care intervention for smoking among 633 low income veterans (Connect to Quit (CTQ), R01-CA141596, PI: Tindle, co-I: Rigotti), we demonstrated that a Chronic Care Model-based coordinated care intervention featuring a dedicated tobacco coordinator substantially increased the use of smoking cessation medication vs. a robust usual care condition without a dedicated coordinator (AOR 3.42, 95% CI (2.42-4.81). 72 The CTQ coordinator was based in the clinical setting, facilitated medication prescriptions via interactions with the PCP and primary care team, and documented care with notes in the EHR. This role resembles that planned for the tobacco coach in the PTCM model.
Quitline eReferral. Working with the North American Quitline Consortium (NAQC), Dr. Tindle has pioneered the development of the eReferral model 12 and demonstrated its feasibility to engage a clinical population of hospitalized smokers at all levels of readiness to quit smoking in one hospital (Am J Prev Med in press, see References). 11 With the standardized Health Level 7, version 3 templates 73 , eReferral can be used by any EHR that is compliant with Meaningful Use Stage 2. For its interoperability and efficiency, this model has been endorsed by NAQC 12 as a potential national standard of care (see letter of support, Bailey). Direct methods of quitline referral such as eReferral, in which quitline staff proactively reach out to smokers, result in higher initial connection rates than less active methods. [74][75][76][77][78][79] Team members from the University of Pittsburgh and Vanderbilt University are participating in the Joint Commission Tobacco Electronic Clinical Quality Measure Task Force (Tob eCQM) to finalize and beta test strategies, including eReferral, to meet the NHQM.

II. SPECIFIC AIMS
Specific Aim: To conduct a randomized controlled comparative effectiveness trial of two strategies to promote smoking cessation in hospitalized patients: (1) Personalized Tobacco Care Management (PTCM) offering smokers 8 weeks of free nicotine replacement therapy (NRT) in hand at discharge and 7 proactive automated contacts over 3 months via interactive voice response (IVR) phone calls followed by email and/or text message and (2) eReferral, a one-time automated referral from the EHR to the state quitline at discharge. The proposed randomized controlled trial will enroll 1350 adult smokers admitted to 3 large hospital systems in 3 U.S. regions (MA, PA, TN) selected to vary in size, type, and region in order to demonstrate the intervention model's potential for dissemination. All patients will receive guideline-based tobacco cessation treatment delivered inhospital by each site's existing Tobacco Treatment Service 23 directed by a team member (Drs. Rigotti, Tindle, Davis). At discharge, subjects will be randomly assigned to PTCM vs. eReferral and followed at 1, 3, and 6 months.

Study Design:
The proposed study is a 2-arm randomized controlled comparative effectiveness trial testing Personalized Tobacco Care Management (PTCM) vs. eReferral ( Figure 2). 1350 smokers admitted to 3 hospitals will be randomly assigned to study arm at discharge and followed at 1, 3, and 6 months. The 1 o study outcome is cotinine-validated 7-day point prevalence tobacco abstinence at 6-months (Aim 1). Analyses will also test the effect of the interventions on use of treatment (Aim 2), hospital re-admissions, and assess their cost-effectiveness (Aim 3).

Figure 2: Study Design
Design Rationale: We omitted a "usual care" or "no treatment" arm because the NHQM standards are likely to make hospitals reluctant to withhold tobacco treatment, and the strength of the evidence makes it ethically inappropriate to do so. Further, the ubiquity of quitlines and spread of EHRs makes it very likely that the eReferral condition will become "standard care" going forward. We decided against comparing eReferral vs. eReferral + PTCM due to concern of confusing subjects with simultaneous post-discharge outreach calls from both IVR and quitline.
Study Sites: Subjects will be recruited from 3 large private non-profit academic hospitals in 3 U.S. regions (Boston, MA, Pittsburgh, PA, Nashville, TN). Table 1 shows the hospital characteristics. All 3 hospitals already have in place established inpatient Tobacco Treatment Services (TTS) directed by members of the study team who are their hospitals' "tobacco champions" and who have strong support from hospital leadership (see LOS from Drs. Slavin, Shapiro, and Mr. Edgeworth). The in-hospital TTS care and post-discharge quitline services are uniform across sites. Innovation: The project's novelty is the creative way in which proven tobacco dependence treatments are adapted to a specific clinical situation (hospitalization) and packaged into two practical models for delivery by and dissemination to hospitals and health care systems. Both interventions provide proactive outreach to sustain tobacco treatment during the transition from inpatient to outpatient care and both interventions meet quality improvement milestones (NHQMs). The interventions innovatively adapt proven treatments into systems that reach smokers during the critical post discharge transition. The project leverages modern communications technology to deliver post-discharge medication and counseling, link inpatient care to community and health care-based treatment, and tailor treatment to smokers' preferences. The interventions align with the evolution of health care delivery by leveraging the EHR's capacity to deliver and track smoking cessation treatment. 43

Subjects
Inclusion criteria: Adult current smokers who are admitted to a study hospital, are seen by a hospital smoking counselor, and plan to try to quit smoking after discharge. Because smokers may reduce tobacco use when ill, current smoking is defined as smoking >1 cigarette in the week before admission and >1 cigarette/day when smoking at baseline rate in the month before admission.

IV. SUBJECT ENROLLMENT
Recruitment and Enrollment: Subjects will be recruited as part of MGH's, VUMC's, and MUH/PUH's standard treatment protocol for inpatients who smoke. All study sites have inpatient TTS programs that purposely resemble the evidence-based 3-step MGH program based on the successful Ottawa Model: 85 (1) Routine smoking status documentation in the EHR at admission by a nurse produces a daily list of smokers sent to the TTS. (2) A trained tobacco counselor visits these smokers to offer brief bedside counseling and medication support. (3) The counselor links the smoker to post-discharge resources by referral to the free state tobacco quitline (using older methods not integrated into the EHR, e.g., fax referral).
At the end of the hospital visit, TTS counselors will screen each smoker for study eligibility, alert eligible patients to the availability of a study offering post-discharge smoking cessation assistance, and ask about interest. The research assistant (RA) will visit a patient at the bedside to verify eligibility, explain the study in detail using a written handout that is given to the patient, and obtain verbal informed consent. Screening for eligibility will include reviewing the TTS counselor's progress note, the admission note, and contacting the patient's nurse and case manager to determine exclusion criteria. If the patient wishes to have more time to consider study participation, he or she will be given the name of the RA and study phone number. Because lengths of stay are short, it is possible that the patient will be discharged before being able to enroll in the study.
Baseline data collection will include demographic factors, admitting diagnosis, admitting service, smoking and quitting history, measures of nicotine dependence (cigarettes smoked/day in month before admission and time to first morning cigarette), intention to remain abstinent from tobacco after hospital discharge, and detailed contact information for the patient and up to 3 close contacts. Some of the data is routinely collected by the TTS counselor and entered into the TTS electronic database. It will be supplemented by additional data collected by the study research assistant at the bedside. The research assistant will use a password protected iPad, connected to the hospital's secure wireless connection, to enter baseline data directly into a RedCap project.
Assignment to Study Arm: Randomization will be stratified by (1) study site, (2) primary admitting diagnosis (cardiac vs. other), and (3) cigarettes/day (>10, <10) to ensure that the treatment groups are balanced on these potential confounders. Prior work identified these significant independent predictors of post-discharge abstinence. After the patient enrolls, the RA will randomly assign the subject to 1 of 2 treatment conditions using the computer-generated randomization scheme created by the study statistician for the corresponding stratum. Subjects will receive a handout describing their assigned treatment condition. Intervention subjects will also receive instruction sheets on how to take nicotine patch, gum, and/or lozenge provided through the study at discharge. The PTCM and eReferral interventions begin at hospital discharge and will continue for 3 months.
Subject Payment: Subject payments are being managed by UPMC's internal/standard study subject payment system -Vincent. Vincent is the next generation of software first created in 2007 as a solution for the payment of compensation to medical study participants. Its unique features and functionality allow for the issuance of anonymous, reloadable, MasterCard-branded, instant-issue, stored value cards with multiple redemption options. Vincent allows for payments to be made in a controlled, auditable, decentralized environment with complete, centralized control and accounting to General Ledger with minimal risk and exposure to staff or clients.
At the time of enrollment, the RA will enter study subjects directly into Vincent's payment system via password protected web interface. The RA will enter the subject's name, address, and SSN (with permission). If the subject does not provide their SSN, they can still receive payment, however, their payment will be reduced by 24% for tax purposes. If the subject's card is lost or stolen a new card will be sent via USPS. The subject will be charged for the cost of the additional card by subtracting the amount ($1.25 from their payment or balance). The balance will be transferred to the new card. Subjects will be informed of these exceptions during the consent process. Once the subject is entered into Vincent payment system, they will receive a Vincent payment card, which will be loaded with payments throughout the study. All participants will receive $20 for each of the 3 follow-up telephone calls (1, 3, 6 months) that they complete, for a total compensation of $60, in addition to $20 for each of the optional qualitative phone surveys at 3-and 6-months. Participants in the PTCM condition will also receive up to 8 weeks of FDAapproved smoking cessation medication and up to 7 free smoking cessation counseling sessions at no cost. At 6 months, all participants who report that they are not smoking will be asked to provide a saliva sample as biochemical confirmation of abstinence or come in to conduct an expired CO reading (if on NRT). If the participant is unable to come in to conduct a CO, then a personal CO device (CoVita iCO Smokerlyzer) will be mailed to the participant to complete the CO reading remotely. Participants will be paid $150 when we receive the saliva sample or the expired CO reading, regardless of whether it confirms nonsmoking.

V. STUDY PROCEDURES
Prior to study enrollment, all subjects will receive standardized in-hospital smoking intervention provided at clinical services at each study site. This infrastructure ensures consistent implementation of the in-hospital treatment and provides ready access to eligible participants at all 3 sites. The PTCM and eReferral interventions begin at hospital discharge and continue for 3 months. Table 2 summarizes how each treatment component is operationalized in each intervention. Each IVR call/email/text will assess: (1) current smoking status and intention to quit, (2) current smoking cessation medication use, and (3) medication side effects. At each contact patients will have the option to request additional support from the tobacco coach; separately, some responses will trigger a call back from the coach. Criteria to trigger a live counseling call will be: (1) patient's request; (2) patients who resumed smoking after discharge but still want to quit; (3) patients who stopped using pharmacotherapy before the end of an 8-week course; (4) patients reporting medication side effects.
• Tobacco Coach: The tobacco coach is the "human face" of the intervention to the patient and performs a dual role as coordinator and counselor. In the coordinator role, the coach will interact with the automated technology platform that makes outbound contacts by IVR, email and/or text message, respond to patients' requests for return calls, and coordinate tobacco treatment with the patients' outpatient primary care team, using the EHR. In the counselor role, the coach will provide brief (10-15 min) supervised protocol-driven behavioral counseling and medication management support upon patient request. In addition, the coach will document in the EHR at study entry and intervention completion (3-months) to the patients' primary care team indicating the patient's study enrollment, interest in quitting, medication dispensed at discharge, and tailored suggestions for addressing smoking. This process ensures that every patient receives cessation support regardless of their response to IVR/email/text outreach. At any outreach contact, patients can request a call back, which will be made within 48 hours. At that call, the coach will (1) offer 10-15 minutes of protocol-driven counseling and medication support, (2) refer the patient to additional free counseling support as needed provided by local resources, phone (state quitline) or text message (enrolling the patient in the National Cancer Institute's free SmokefreeTXT program), (3) facilitate additional medication requests by documenting in the patient's encounter in the EHR and requesting additional smoking cessation medications. The tobacco coach will follow a detailed protocol to provide motivational, cognitive-behavioral smoking cessation and relapse prevention tools, tailored to the smoker's characteristics and provide medication management and adherence support, with the goal of completing a full course of cessation medication. 70 Each site's PI (a physician) or delegate will provide clinical supervision for the coach. Each coach will complete the University of MA online basic tobacco cessation training course and in-person 4-day Core Training course (or equivalent), 86 and 6 hours of observing the site's senior CTTS counseling inpatient smokers. Sites will have monthly (or as needed) case reviews to provide a forum for working through challenging clinical scenarios. Post-discharge counseling will be evaluated by the site's PI or delegate to ensure that counselors are completing relevant counseling modules, necessary database documentation, and adhering to principles of Motivational Interviewing (MI). Completion of HH4 counseling modules and HH4 database documentation will be used to measure "what" is discussed during a counseling session. Monitoring and coding HH4 post-discharge counseling calls, using the Brief Intervention (BI) Checklist and The Motivational Interviewing Treatment Integrity (MITI) Coding Manual 4.2.1 (Moyers, et al., 2014), will be used to measure "how" post-discharge counseling is being delivered. The site's investigator or delegate will randomly select days for monitoring counseling calls, totaling 5% of their cases, and code each counseling session using the BI checklist and MITI 4. The site's investigator or delegate will also review documentation in database (DB) to ensure that the counseling module selected in the DB is consistent with the counseling content discussed during the call and that necessary database documentation is completed. Permission to audio record or listen to counseling calls will be obtained when the coach initiates the counseling call with the patient (refer to HH4 Audio Recording-Monitoring Verbal Consent). For audio recording, a small tape recorder on speakerphone or other technology, if available, will be used to tape counseling calls. No identifiers will be used, digital files will be transcribed, and tapes (or digital files) will be destroyed after the study. For realtime monitoring, the site's investigator or delegate will listen to the counseling call when it is taking place.
• Smoking Cessation Medication: At hospital discharge, smokers receive a free standard 8-week course of treatment of their choice of nonprescription NRT (patch, gum, lozenge or a combination of patch + gum or lozenge). The drug regimen can be a continuation of NRT started in the hospital or be new at discharge. Patients in the HH1 and HH2 trials had a choice of any FDA-approved cessation medication and 95% used NRT. Only NRT is used in this trial for simplicity. We include combination NRT because some but not all studies have found it to outperform single NRT. 2,87 Following a protocol and with patient input, the inpatient TTS counselor selects NRT product and dosage, which the hospital physician must approve and prescribe. NRT is delivered to the patient before discharge with written information on use and side effects. This workflow was successful in HH2. It resembles new "Meds to Beds" 88-90 programs being implemented in the study hospitals, providing an avenue for future sustainability. 11 using Direct, a national encryption standard for securely exchanging clinical healthcare data (Figure 3). Quitlines offer free cessation support (counseling and often an NRT sample) to U.S. smokers who call a toll-free number. 13,14 Proactive telephone counseling is an efficacious smoking cessation treatment method that incorporates motivational interviewing, cognitive-behavioral counseling, and relapse prevention strategies, usually in a multi-session call format. 9,91,92 For the study, the RA enrolling the patient will make the eReferral from the EHR at discharge. Quitline staff will then attempt to contact the smoker by phone within 72 hours to offer the standard services offered by the state quitline (multiple-call counseling protocol and 4 weeks NRT). 12,73 Up to 3 contact attempts are made but in practice successful connection may take several weeks. A report of the quitline referral is sent securely to the EHR where the patients' primary health care team can access it and act upon it as needed. In accordance with best practices for Federal Health IT as determined by the Office of the National Coordinator for Health Information Technology, eReferral employs standardized recommendations for message structure, content, transport, and delivery to maximize interoperability. The standardized data elements facilitate quality improvement and reporting metrics for NHQM. The quitline provider for this study, National Jewish Health (NJH), currently serves all MA and PA patients under state contract 93 and will also serve Vanderbilt study participants to ensure uniformity of eReferral across sites.

Data Collection
Baseline data: Each site's RA will do a baseline survey after enrollment and collect contact information for the patient and up to 3 close contacts in order to minimize loss to follow-up. To minimize burden on hospitalized subjects, some data will be obtained from hospital records and the standardized data collection form used by smoking counselors who provide inpatient counseling at each site. Smoking counselors and RAs will be trained to ensure that they complete data forms consistently across all sites.
Blood collection for future potential genetic analyses (Vanderbilt site only): The NIH's precision medicine initiative, All of Us, aims to understand how genetics, in conjunction with a person's environment and lifestyle, can optimize prevention and treatment of illness. The GSCAN results recently published in Nature Genetics 115 identified hundreds of new genetic variants related to smoking initiation, rate, maintenance, and cessation. New information continues to become available regarding the role of genetic variation in smoking cessation and response to pharmacotherapy. The Vanderbilt University Medical Center (VUMC) site study staff will initiate a protocol to collect a blood sample on newly-enrolled and consented participants for genotyping (GWAS). The updated informed consent document thoroughly incorporates language recommended by NIH guidelines for genetic studies https://osp.od.nih.gov/wp-content/uploads/NIH_GDS_Policy.pdf. For participants who consent to provide a genetic sample, a single blood sample of approximately 15 ml (3 teaspoons) will be collected at the bedside by clinical phlebotomy/study staff.
Outcome assessment: Outcome assessments for all sites will be conducted at 1, 3, and 6 months after hospital discharge by RedCap-initiated surveys, MGH-based study staff, and mailed survey (6-month). In response to the coronavirus, a separate RedCap survey will be administered to all patients enrolled in the study who have not withdrawn or died to explore the impact of coronavirus on tobacco use behaviors and related constructs. Study participants will receive $20 uploaded to their payment card for completing this optional coronavirus survey. Study participants will select preferred method/s of contact (Participant Contact Sheet). RedCap follow-up surveys will be accessible through a password protected link sent to subjects by email and/or text message. Subjects can click on the link via computer or mobile device. Participants who do not complete the assessment by email or text, will be contacted by MGH study staff and mailed survey (6month survey only). If participants cannot be reached, study staff will reach out to subjects' alternate contacts to find newer contact information. Subjects will receive $20 uploaded to their payment card (provided at enrollment) for each follow-up assessment completed. An additional audio-recorded qualitative survey will be offered to participants at 3-and 6-months to solicit feedback about participants' experience in participating in the study.
In addition to the HH4 Quantitative COVID Survey and HH4 Qualitative Interview (AMEs 36-38), study investigators will leverage the parent study's existing partnership with the large US state quitline operator, National Jewish Health (NJH) to address much larger population-based statewide samples. Approximately 16,000 individuals, during a one-year period, who smoke and/or vape and who are calling their state quitline in Massachusetts (MA), Pennsylvania (PA), Kentucky (KY), and Minnesota (MN) for help during the pandemic will be asked 3 questions to assess COVID-19 pandemic-related effects on their risk perceptions, motivation, and smoking and/or vaping behavior. These questions harmonize with the existing HH4 Quantitative COVID Survey. Survey questions will be administered by trained quitline staff as part of the standard intake process (web or phone). Data will be maintained by NJH with permission of the Departments of Health in each state, who consider the COVID-19 related survey questions to be part of quitline care (i.e., not requiring informed consent). The HH4 team will analyze de-identified aggregated state quitline data provided by NJH. With quitline data, investigators will explore the impact of coronavirus on individuals' risk perception, change in motivation to quit, change in tobacco use, and engagement in treatment resources, as well as explore 6-month quit rates during the pandemic as compared to 1 year earlier, adjusting for any imbalance in caller characteristics.

Measures Intervention Effectiveness: Smoking Cessation
1 o Outcome measure: Verified 7-day point prevalence tobacco abstinence at 6-month follow-up The proposed measure is self-reported abstinence from all tobacco products (including electronic cigarettes) for the past 7 days, confirmed by a saliva cotinine of <10 ng/ml or CO<9 ppm, which are consensus values. 96,97 We will obtain saliva samples by mail, an accepted method. 98 Our definition of tobacco abstinence does not allow for e-cigarette use because the FDA has deemed e-cigarettes to be tobacco products 99 , but it allows for NRT use, as recommended. 96 Because of uncertainty about the risk/benefit of e-cigarettes for cessation, we will calculate a secondary tobacco abstinence measure that allows for use of e-cigarettes but no other tobacco products. (In the HH2 trial, the alternative calculation produced very small differences in abstinence rates that did not change study results.) Because NRT use produces a false positive cotinine, the biochemical validation criterion for a patient reporting NRT use at 6 months will be an expired-air carbon monoxide measurement of <9 ppm, obtained at an in-person visit. 100 Subjects who self-report smoking, do not provide a saliva sample or CO measurement, whose cotinine or CO measures exceed the cut-offs, or who are lost to follow-up at 6 months will be counted as smokers. 96,97,100 Obtaining saliva samples in low-contact intervention trials, including recent studies in hospitalized smokers, is challenging. 55,101 We will offer a $150 incentive uploaded to their payment card for return of a sample, which produced a 69% return rate in HH2 (with no difference by study arm).
2 o Outcome measures of tobacco use: to be calculated using standard definitions. 96 • Self-reported 7-day and 30-day point prevalence tobacco abstinence at 1 month, 3 months, 6 months • Sustained [repeated point prevalence] tobacco abstinence (= self-reported abstinence at 1, 3, and 6 months) • Duration of continuous tobacco abstinence after hospital discharge (self-report)

Engagement in Tobacco Cessation Treatment
• Proportion of participants who use smoking cessation counseling or pharmacotherapy after discharge • Duration (days) of medication use, number of counseling contacts after discharge Definitions: Counseling can be from any evidence-based source, including clinicians, and occur in person, by phone or text message. Neither quitline registration calls nor IVR calls will be counted as counseling, but speaking to a tobacco coach at either the quitline or hospital will count. Medication includes all FDA-approved smoking cessation medications.
To succeed in promoting tobacco abstinence, post-discharge interventions must engage patients in tobacco treatment. To do so, they must reach patients after discharge, and patients must agree to use evidence-based pharmacotherapy and/or counseling. Table 3 shows how we will measure these concepts, using a combination of patient self-reports at each assessment and records of treatment offer or delivery obtained from TelASK (IVR vendor), NJH (quitline), and SmokefreeTXT internal monitoring systems as well as from the EHR. EHR data will include (1) quitline feedback reports; (2) tobacco coach records of patient contact and coordination of care activities; (3) pharmacy records of NRT prescriptions provided by the study; (4) use of SmokefreeTXT. (Usage data from SmokefreeTXT will be visible to the tobacco coach in the EHR through the Epic-Smokefree.gov interface that is currently being programmed and will be publically available by 2017 (personal communication with Dr. Erik Augustson, Smokefree.gov Director). This approach utilizes the capacity of EHRs to capture data on tobacco treatment use for assessing the outcomes of interventions and illustrates how tobacco treatment interventions can be integrated into EHRs. Health and health care utilization outcomes All-cause hospitalizations, cardiac and respiratory hospitalizations, all-cause deaths over 1 year. We will compare rates of hospitalizations and mortality in the two study arms. These will be secondary, exploratory analyses. There is some evidence that hospital-initiated tobacco treatment programs can reduce readmissions by 30 days and mortality by 1 year follow-up. 38 At all follow-up surveys, we will ask subjects about subsequent hospital admissions, using standard items from the National Health Interview Survey. To corroborate patient reports, we will review administrative data from our hospitals and ask permission to review the discharge summaries from any admission to an outside hospital. Among subjects lost to follow-up, mortality will be detected via proxy contacts, by reviewing hospital records, and, if necessary, the National Death Index.
• *Depressive symptoms: 8-item Center for Epidemiologic Studies Depression Scale 104 at baseline and follow-up. Rationale: depression is common in smokers, 105 depressive symptoms predict postdischarge relapse. 106 • *Alcohol use: AUDIT-C, 107 a 3-item survey assessing frequency, quantity, and binge drinking.
Rationale: heavy alcohol use is associated with difficulty quitting. • *Other substance use: Any past month use. Rationale: other substance use is common in smokers and may be associated with lower quit rates after treatment.
Implementation and Process Measures. Data at each site will be collected to monitor rates of study eligibility, refusal, intervention delivery, and follow-up completion, using the following RE-AIM model constructs. 108 Reach: % of identified smokers admitted during the study who are seen by a TTS counselor, are eligible for the study, and enroll. Effectiveness: the 1 o trial outcome. Implementation: % of subjects assigned to each study arm who receive relevant components (See Table 3). These data will be obtained from TelASK, NJH, and SmokefreeTXT internal monitoring systems as well as from the EHR.

Statistical methods Sample Size
A total sample of 1350 (675/group) will have 84% power to detect a 6.5% absolute difference in primary outcome, verified 7-day point-prevalence abstinence at 6 months, assuming rates of 16.5% (eReferral group) and 23% (PTCM group), and a 2-tailed type I error rate of .05. The rate ratio (1.39 =.23/.165) is clinically meaningful and resembles the ratio found in the Cochrane meta-analysis of smoking cessation interventions for hospitalized patients. 2 Rationale: eReferral: We conservatively estimate the abstinence rate from the HH2 trial (17% and 16%) 56 ; patients in both conditions were referred to a quitline. PTCM: Intervention resembles that of HH1 (25% abstinence rate); 39 we conservatively estimate 23%.

VII. RISKS AND DISCOMFORTS
The potential risks to subjects include potential psychological distress from speaking with a counselor or answering questions about their smoking, and a loss of confidentiality of their healthcare data. In addition, those patients who are randomly assigned to receive a free supply of FDA-approved smoking cessation medication may be subject to the potential side effects of using nicotine replacement therapy (NRT).
• Nicotine patch: The most common side effect is irritated skin where the patch is applied, which is commonly managed by rotating patch sites and/or applying an OTC corticosteroid cream (such as 1% hydrocortisone). In rare cases nausea, dizziness, tachycardia can occur. Nicotine patches are sold without prescription in the U.S., which is an indication of the FDA's view of their relative safety. • Nicotine gum or lozenge: The most common side effects are sore jaw, sores in the mouth, hiccups, dyspepsia, and nausea. In rare cases nausea, dizziness, or tachycardia can occur. Many of the side effects of the gum are the result of chewing the gum improperly and can be avoided by proper technique of the gum. Nicotine gum and lozenges are sold without prescription in the U.S., which is an indication of the FDA's view of their relative safety. Other risks: Participants are at some risk for loss of privacy/confidentiality. If patients opt to receive phone calls on a shared phone, a family member may inquire about the nature of the phone calls. Study staff will not disclose information about participants' participation in the study to others who share a phone line with participants. They will leave the minimum amount of information necessary on participant answering machines.
There is a risk of counseling bringing up issues that are upsetting to participants. Counselors will do their best to be supportive to patients. In addition, participants will be told that they can refuse to answer any questions or terminate contact with counselors at any time.

VIII. POTENTIAL BENEFITS
Participants in this study may benefit by being connected better to effective tobacco treatment resources after hospital discharge. They will receive up to 8 weeks of FDA-approved smoking cessation medication at no cost. As a result, they may be helped to quit smoking. Generally, there is nothing better for smokers' health than stopping smoking.

IX. MONITORING AND QUALITY ASSURANCE
Data Monitoring Plan: Study staff will provide TelASK Technologies, Inc., the vendor who will conduct outreach attempts via IVR call/email/text message with patient names and relevant contact information. This information will be transferred bi-directionally through a secure FTP. During the study, TelASK will establish a secure website interface to the data management system in which study staff can view outreach and outcome results in real time.
Data quality (including visits completed during intervention window, missing data, and recruitment rates) will be monitored monthly by the database manager, Dr. Susan Regan, and systemic data problems will be reported to the PI. IVR calls, emails, and text messages provided by TelASK, Inc. will be monitored for quality assurance. In addition, the Project Manger will review 10% of the counseling progress notes for adherence to the protocol. Outcomes data will be analyzed by Dr. Yuchiao Chang, a biostatistician, using logistic regression and survival analysis. The alpha level will be set at 5%. Interim data analysis will be conducted halfway through the trial and results will be reported in the annual NIH progress report.
The principal investigator, Dr. Rigotti, and the Project manager will be responsible for monitoring the safety and effectiveness of this trial, executing the data safety and monitoring (DSM) plan, and complying with reporting requirements. Dr. Rigotti will supply a summary of the DSM report to the NIH on an annual basis as part of the progress report.

Safety Monitoring Plan:
The main risks to participation in the study include the potential for psychological discomfort during counseling sessions and side effects to the FDA-approved medications. We will protect against risks of psychological discomfort by using language that is meant to offer assistance and promote health, rather than demonstrate blame or guilt. In order to protect against risk from pharmacotherapy usage, these steps will be taken: (1) Medication is being provided only to patients in the PTCM intervention arm. These participants also receive automated telephone calls by IVR 7 times in the 3 months after hospital discharge, especially soon after discharge (at 3 days and 2, 4, 6, 8, 10, and 12 weeks). At each call, patients are specifically asked about any side effects or problems. Those who report them are advised to speak to a live tobacco counselor. Patients who request a medication refill after the initial 30 day supply are required to speak to a live counselor, who asks about medical problems before authorizing a refill of medication. Study staff will be required to report any unexpected or questionable reports of adverse effects to the study PI (Dr. Rigotti). These will be reviewed at the weekly study staff meeting. If more urgent, the PI will review immediately.
(2) The study PI (Dr. Rigotti) will review provide back up to study staff for all medical questions that arise during participant enrollment or study progress.
(3) The study PI (Dr. Rigotti) will review any serious adverse events and report them appropriately to the IRB. SAEs that represent hospital readmissions are anticipated to be frequent in this population of patients with medical illness. Each will be reviewed by the study PI to ensure that the readmission is not related to study medication.
Adverse Events Reporting: Participants who report any adverse events to the smoking counselor will be advised to discuss these side effects with their doctor. The reports of the adverse events will be summarized and reviewed by the PI on a monthly basis and reported to the IRB upon renewal of approval and to the funding agency upon continuing review. Serious adverse events will be reported immediately to the PI who will contact the participant, the participant's physician and the IRB.